RAPGEF2
Description
The RAPGEF2 (Rap guanine nucleotide exchange factor 2) is a protein-coding gene located on chromosome 4.
Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene. RAPGEF2 is a cyclic AMP binding protein.
== Function == Members of the RAS subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs) such as RAPGEF2 serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation.
RAPGEF2 functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. It serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. RAPGEF2 also acts as an effector for Rap1 by direct association with Rap1-GTP, leading to the amplification of Rap1-mediated signaling. It shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to Ras activation through the G(s)-alpha signaling pathway. RAPGEF2 is involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long-term melanogenesis by reducing dendrite extension and melanin synthesis. It provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent manner. RAPGEF2 regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent of both PKA and RAPGEF3/RAPGEF4. It is involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure, and the hippocampal commissure during brain development. RAPGEF2 is involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. It plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. RAPGEF2 may be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}
RAPGEF2 is also known as CNrasGEF, NRAPGEP, PDZ-GEF1, PDZGEF1, RA-GEF, RA-GEF-1, RAGEF, Rap-GEP, nRap GEP.
